Low-molecular weight lanthanide contrast agents: Evaluation of susceptibility and dipolar effects in red blood cell suspensions

Red blood cell (RBC) suspensions, containing low-molecular weight (LMW) dysprosium (Dy) and gadolinium (Gd) chelates, were selected as a two-compartment system for the evaluation of the magnetic dipolar and susceptibility contributions to the transverse (T2) relaxation of solvent water protons. The influence of RBC geometry and degree of metal chelate compartmentalization on T2 was investigated by variation of the osmolality and hematocrit (HC), respectively. The T2-relaxation ability of Dy-chelates was markedly improved in RBC suspensions, in comparison to aqueous solutions, due to the presence of susceptibility effects that more than compensated for the low dipolar relaxation efficacy. Despite a smaller susceptibility effect, the Gd-chelates were still the most efficacious in shortening T2 due to their comparatively larger dipolar relaxation contribution. The results obtained with the Dy-chelates allowed the evaluation of the relative contributions of susceptibility and dipolar mediated relaxation for the Gd-chelates. The RBC geometry and degree of compartmentalization influenced strongly the T2 relaxation efficacy of Dy-chelates, as opposed to the Gd-chelates. Hemolysis eliminated the susceptibility effect, essentially removing the T2 relaxation ability of Dy-chelates. The T2 relaxation efficacy of Gd-chelates was improved by hemolysis due to enhancement of the dipolar relaxation. As a conclusion, RBC suspensions have clearly been shown to be a suitable ex vivo model with which to distinguish the different contrast mechanisms of LMW Dy- and Gd-based MRI contrast agents.